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Tet and TDG Mediate DNA Demethylation Essential for Mesenchymal-to-Epithelial Transition in Somatic Cell Reprogramming
文献类型：期刊论文
| 作者 | Hu, X; Zhang, L; Mao, SQ; Li, Z; Chen, JK; Zhang, RR; Wu, HP; Gao, J; Guo, F; Liu, W |
| 刊名 | CELL STEM CELL
 |
| 出版日期 | 2014 |
| 卷号 | 14期号:4页码:512-522 |
| 通讯作者 | Xu, GL (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai Key Lab Mol Androl,State Ke Lab Mol Biol, Shanghai 200031, Peoples R China.,glxu@sibs.ac.cn |
| 英文摘要 | Tet-mediated DNA oxidation is a recently identified mammalian epigenetic modification, and its functional role in cell-fate transitions remains poorly understood. Here, we derive mouse embryonic fibroblasts (MEFs) deleted in all three Tet genes and examine their capacity for reprogramming into induced pluripotent stem cells (iPSCs). We show that Tet-deficient MEFs cannot be reprogrammed because of a block in the mesenchymal-to-epithelial transition (MET) step. Reprogramming of MEFs deficient in TDG is similarly impaired. The block in reprogramming is caused at least in part by defective activation of key miRNAs, which depends on oxidative demethylation promoted by Tet and TDG. Reintroduction of either the affected miRNAs or catalytically active Tet and TDG restores reprogramming in the knockout MEFs. Thus, oxidative demethylation to promote gene activation appears to be functionally required for reprogramming of fibroblasts to pluripotency. These findings provide mechanistic insight into the role of epigenetic barriers in cell-lineage conversion. |
| 学科主题 | Cell Biology |
| 类目[WOS] | Cell & Tissue Engineering ; Cell Biology |
| 关键词[WOS] | PRIMORDIAL GERM-CELLS ; POSTNATAL-DEVELOPMENT ; MAMMALIAN DNA ; 5-HYDROXYMETHYLCYTOSINE ; METHYLATION ; PROTEINS ; GENOME ; 5-CARBOXYLCYTOSINE ; PLURIPOTENCY ; ROLES |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000334766400014 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/177]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Hu, X,Zhang, L,Mao, SQ,et al. Tet and TDG Mediate DNA Demethylation Essential for Mesenchymal-to-Epithelial Transition in Somatic Cell Reprogramming[J]. CELL STEM CELL,2014,14(4):512-522. |
| APA | Hu, X.,Zhang, L.,Mao, SQ.,Li, Z.,Chen, JK.,...&Xu, GL.(2014).Tet and TDG Mediate DNA Demethylation Essential for Mesenchymal-to-Epithelial Transition in Somatic Cell Reprogramming.CELL STEM CELL,14(4),512-522. |
| MLA | Hu, X,et al."Tet and TDG Mediate DNA Demethylation Essential for Mesenchymal-to-Epithelial Transition in Somatic Cell Reprogramming".CELL STEM CELL 14.4(2014):512-522. |
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